Continuation of Grant GM 24749 is requested to continue experimental and theoretical studies on the selective ion permeation through peptide channels and carries across lipid bilayer membranes to provide a foundation for understanding, at a molecular level, the ion selectivity and permeation mechanisms of nerve. For channels, we propose to continue studies on selectivity among nonvalent cations for the Gramicidin A channel, extending these to theoretical investigations of multi-site, multi-barrier single filing models and experiments designed to distinguish between alternative models. These studies should extend the basis laid by Hille and Armstrong for using cations as "probes" of the structure of the Na ion and K ion channels of nerve, extending this to the selectivity filters as well as the binding sites. For carriers, we propose to apply the well advanced theories to the analysis of structure-function relationship in a series of synthetic cyclic and non-cyclic peptide carriers of cations and anions. Novel Li ion and selective and Na ion selective carriers, as well as proline analogs of Valinomycin, will be emphasized. These offer the possibility to understand the functional significance of different amino acid side chains, which should be pertinent to the selectivity of membrane proteins. We will apply a judicious blend of theoretical development and experimental characterization to reconstituted membrane systems of known chemical composition and well-defined structure, made from normally occurring membrane constituents with the goal ultimately of developing a truly molecular understanding of the ion selectivity and permeation processes of the Na ion and K ion channels of nerve.